Origin of cancer common in people with HIV points way to therapy

A virus turns lymph vessel cells into a cancer that affects people with weakened immune systems, according to research published in Nature Genetics1.

A Cancer Research UK team based at University College London have discovered that Kaposi sarcoma - which is common in people who are HIV positive or have had an organ transplant - first develops in the inner cell lining of lymph vessels, the transport network for the body's immune system.

The findings indicate that drugs arresting the development of cells lining lymph vessels could prove powerful against Kaposi sarcoma. They could also yield a test for doctors to predict which patients are likely to develop this cancer.

Kaposi sarcoma typically appears as coloured lesions or blotches on the skin, although it can spread to internal organs.

The sarcoma is the most common cancer in individuals with HIV or AIDS and for that reason is the most common cancer in many Sub-Saharan African countries. It is also one of the most common cancers in patients who have had their immune system suppressed to lower the likelihood that their bodies will reject a transplanted organ.

Professor Boshoff, who is joint Director of the Cancer Research UK Viral Oncology Group at UCL, says: "The cell type in which Kaposi sarcoma first develops has been a mystery since it was discovered in 1872.

"We analysed the genetic makeup of Kaposi sarcoma cells and found they are most similar genetically to cells of the inner lining of lymph vessels, known as lymphatic endothelial cells."

The research was funded by Cancer Research UK, with additional funding from the Medical Research Council and the Wellcome Trust.

The team also found that the virus that causes Kaposi sarcoma - the Kaposi sarcoma herpes virus (KSHV) - can turn the endothelial cells that line blood vessels into cancerous lymphatic endothelial cells.

Professor Boshoff adds: "We have shown for the first time that a virus can genetically reprogramme blood vessel endothelial cells into lymphatic endothelial cells, and that it is these lymphatic cells that develop into Kaposi sarcoma."

"Now that we know in which type of cell Kaposi sarcoma originates, we should be able to identify new ways to treat the condition. The findings could also yield new clues about other cancers that are triggered by viruses, such as cervical cancer."

The new study suggests that drugs inhibiting the growth of the lymphatic endothelium could prove a successful new way of combating Kaposi sarcoma. Such drugs are already being developed.

The research also points towards a new predictive test for Kaposi sarcoma.

The team found that high levels of circulating growth factors which encourage lymphatic endothelial cells to proliferate were strongly associated with the development of Kaposi sarcoma.

Professor Boshoff adds: "Finding new cancers early is vital if treatment is to be successful. By testing blood for growth factors that encourage the cells lining lymph vessels to grow, doctors might be able to predict which high-risk patients - such as those with HIV or who have had an organ transplant - will subsequently develop Kaposi sarcoma."

Professor Robert Souhami, Director of Clinical and External Affairs at Cancer Research UK, says: "People with HIV or who are taking immunosuppressive drugs are particularly susceptible to cancer."

"Chris Boshoff and his team's discovery that Kaposi sarcoma originates in the cellular lining of lymph vessels furthers our understanding of the disease and also has strong therapeutic implications.

"This is a good example of how research into the basic workings of cells and viruses can open new avenues of opportunity for treatment."

ENDS

Nature Genetics36 (7)

Notes to Editor

Kaposi sarcoma causes tumours to develop in the tissues below the skin surface, or in the mucous membranes of the mouth or nose. The lesions appear as raised blotches or nodules that may be purple, brown or red in colour.

Whereas most cancers begin in one place in the body and may then spread around the body, Kaposi sarcoma can appear in several parts of the body at the same time.

Kaposi sarcoma commonly disappears if the immune system is restored. It can otherwise lead to potentially fatal intestinal and lung lesions.

Scientists are currently trying to understand Kaposi sarcoma better in order to find new ways of treating it in patients whose immune systems are chronically low.

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